The incorporation of 3H-leucine into guinea pig thyroglobulin was studied in vivo. The kinetic results thus obtained were tested against various models of synthesis by computer analysis. The only models yielding a satisfactory fit to the data contained two compartments for the synthesized thyroglobulin. The compartments differed in their turnover rate of thyroglobulin, the first compartment having a much faster turnover rate than the second. These results suggest that the bulk of the daily requirements of thyroid hormone in the peripheral tissue originates from newly synthesized thyroglobulin, not the older, more heavily iodinated thyroglobulin in the lumen.